chr22-50275962-G-T

Variant names:

• chr22-50275962-G-T
• rs1309378692
• NM_012401.4:c.5339C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012401.4(PLXNB2):​c.5339C>A​(p.Ala1780Glu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 15/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1780V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLXNB2 NM_012401.4 missense, splice_region
• Scores: Splicing: ADA: 0.02328
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00
• Publications: 0 publications found

Genes affected

PLXNB2 (HGNC:9104): (plexin B2) Members of the B class of plexins, such as PLXNB2 are transmembrane receptors that participate in axon guidance and cell migration in response to semaphorins (Perrot et al. (2002) [PubMed 12183458]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNB2	NM_012401.4	c.5339C>A	p.Ala1780Glu	missense_variant, splice_region_variant	Exon 36 of 37	ENST00000359337.9	NP_036533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNB2	ENST00000359337.9	c.5339C>A	p.Ala1780Glu	missense_variant, splice_region_variant	Exon 36 of 37	5	NM_012401.4	ENSP00000352288.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.046	T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.092
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D;.
M_CAP	Benign	0.0065	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L
PhyloP100		5.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.24	N;N
REVEL	Benign	0.25
Sift	Benign	0.29	T;T
Sift4G	Benign	0.46	T;T
Polyphen		0.55	P;P
Vest4		0.57
MutPred		0.43		Gain of disorder (P = 0.0286);Gain of disorder (P = 0.0286);
MVP		0.31
MPC		2.0
ClinPred		0.79	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.22
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.023
dbscSNV1_RF	Benign	0.15
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1309378692; hg19: chr22-50714391;